Research

Our Research

The Koike Lab investigates how cellular, tissue, and inter-organ networks change with age and how these changes can be modulated to restore function. We focus particularly on the hematopoietic and autonomic nervous systems and develop multicellular organoid models to reconstruct and analyze age-related changes in human tissues.

1. Hematopoietic Stem Cell Aging and Niche Regulation

Hematopoietic stem cells continuously generate blood and immune cells throughout life. With age, their cellular state and differentiation balance change, contributing to impaired hematopoietic and immune function.

We study not only hematopoietic stem cells themselves but also the surrounding cellular and molecular environment, or “niche,” that regulates their behavior. By combining in vivo models, cell culture, flow cytometry, and single-cell analyses, we aim to identify age-associated alterations in stem cell–niche interactions and explore strategies to restore hematopoietic function through niche regulation.

Age-associated changes in hematopoietic stem cells and their bone marrow niche.

2. Aging of the Autonomic Nervous System and Organ Function

The autonomic nervous system innervates organs throughout the body and continuously regulates their function in response to physiological and environmental changes. Age-associated alterations in neural regulation may therefore affect not only individual organs but also systemic networks involving the nervous, vascular, and immune systems.

We focus particularly on sympathetic nerves and investigate how age-related changes in neural structure and function influence tissues such as the liver, skeletal muscle, and bone marrow. Using in vivo models, tissue imaging, flow cytometry, and single-cell and spatial analyses, we aim to define neurovascular and neuroimmune interactions that contribute to age-related functional decline and recovery.

Age-related changes in autonomic neural regulation and their effects across multiple organs.

3. Modeling and Modulating Aging with Multicellular Organoids

Human aging is not a cell-autonomous process. It emerges from coordinated changes and interactions among epithelial, stromal, vascular, immune, and neural cell populations. Directly observing and experimentally manipulating these processes in human tissues remains challenging.

We develop multicellular organoids and integrated tissue models from human iPS cells and primary cells to reconstruct age-associated changes in cellular states, tissue architecture, and cell–cell communication. By combining these models with imaging, transcriptomic, single-cell, and spatial analyses, we aim to identify mechanisms that drive aging and establish experimental platforms for evaluating factors and interventions that may restore tissue function.

Multicellular organoid models for reconstructing and manipulating age-associated tissue changes.

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